My research objective is the elucidation of the metabolism of folates in the erythrocyctic stages of malarial parasites. This is of interest and significance because of possible host-parasite interactions in folate metabolism and chemotherapy of malaria. My work from 1968-1971 at Rockefeller University with Plasmodium lophurae has provided strong evidence for the operation of a "thymidylate synthesis cycle" which fits well with the work of others on purine and pyrimidine metabolism in malaria. On the basis of previous studies, it is proposed to extend these studies in the following ways: (1) Further characterization of serine hydroxymethyltransferase in P. lophurae; (2) Direct confirmation of serine-3-14C incorporation into DNA of P. lophurae; (3) Study of folate enzymes and "thymidylate synthesis cycle" in other malarial species and their host erythrocytes; (4) Study of the transport of p-aminobenzoic acid, pteridines, and folates into normal and infected erthrocytes and free parasites of P. lophurae and other malarial species. These studies are designed to investigate the general relevance of the "thymidylate synthesis cycle" and provide comparative information on the importance of exogenous p-aminobenzoic acid, pteridiness, and folates in the nutritional physiology of malarial parasites. This information will have importance in chemotherapy and further the understanding of interrelations between the intracellular parasite and its host cell in the conversion and utilization of folates.